Advances in Genetics最新文献

Advancements in informatics, genetics, and neuroscience have greatly expanded our understanding of how the central nervous system (CNS) regulates energy balance and metabolism. This chapter explores the key neural circuits within the hypothalamus and brainstem that integrate behavioral and physiological processes to maintain metabolic homeostasis. It also examines the dynamic interplay between the CNS and peripheral organs, mediated through hormonal and neuronal signals, which fine-tune appetite, energy expenditure, and body weight. Furthermore, we highlight groundbreaking research that unveils molecular and cellular pathways governing energy regulation, representing a new frontier in addressing obesity and metabolic disorders. Innovative approaches, such as neurogenetic and neuromodulation techniques, are explored as promising strategies for improving weight management and metabolic health. By providing a comprehensive perspective on the mechanisms underlying energy balance, this chapter underscores the transformative potential of emerging therapeutic innovations.

The post-genomic era has ushered in a transformative shift in biomedical research, driven by the integration of multi-omics technologies and advanced computational tools. While genome-wide association studies (GWAS) have identified thousands of variants linked to complex traits and diseases, the majority of these lie in non-coding regions, where their functional roles remain elusive. This chapter explores how fine-mapping, functional genomics, and systems biology are converging to bridge this gap, moving from statistical associations to mechanistic insights. Using celiac disease as a model, we illustrate how genomic, transcriptomic, epigenomic, and proteomic data can be harmonized to identify causal variants, prioritize candidate genes, and map regulatory networks that drive disease pathogenesis. We highlight the power of fine-mapping in refining GWAS signals and the importance of integrating chromatin accessibility, QTL colocalization, and single-cell omics to contextualize genetic risk within specific cellular environments. The chapter also discusses the promise of polygenic risk scores, the role of metabolomics in capturing functional phenotypes, and the emergence of single-cell and spatial technologies in revealing disease heterogeneity. Despite these advances, challenges remain-including data heterogeneity, computational complexity, and the underrepresentation of non-European populations in genomic studies. Addressing these issues will be critical for ensuring the equity and clinical utility of precision medicine. Ultimately, this chapter underscores the transformative potential of translational genomics. By connecting genetic variation to molecular function and clinical outcome, multi-omics approaches are paving the way for more predictive, preventive, and personalized healthcare-particularly in the context of autoimmune and other complex diseases.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor dysfunctions. Its pathological hallmark is the aggregation of ɑ-synuclein in the central nervous system (CNS), leading to widespread loss of dopaminergic neurons in the substantia nigra (SN). Interestingly, metabolic disorders localized in the periphery, such as diabetes mellitus, frequently co-occur with PD. Emerging evidence highlights a bidirectional relationship: metabolic diseases may accelerate PD progression, while PD can exacerbate metabolic dysfunction. Beyond these associations, a growing body of research suggests that dysfunction in the peripheral nervous system, the primary communication bridge between the brain and peripheral organs, plays a critical role in these comorbidities. Autonomic nerve perturbation may accelerate dopaminergic neuronal loss in the SN and exacerbate metabolic dysregulation. This chapter synthesizes current evidence linking autonomic dysfunction with the progression of PD and related metabolic disorders, and it explores innovative therapeutic strategies leveraging this bidirectional relationship to address PD progression.

Food cravings, an intense desire to consume specific foods, are a complex interplay of cognitive, emotional, behavioral, physiological, and cultural factors. Although prevalent across genders, food cravings are more frequent and intense in women, with hormonal fluctuations-particularly during the menstrual cycle and pregnancy-playing a significant role. Pregnancy, marked by profound hormonal and physiological shifts, often heightens cravings, likely as a response to the increased metabolic needs of both mother and fetus. However, the tendency to crave high-calorie, palatable foods during this time can lead to excessive weight gain, presenting potential risks to both maternal and fetal health. This chapter examines the neural mechanisms underlying altered eating behaviors during pregnancy and their role in triggering food cravings. We discuss the health implications of disrupted eating patterns in pregnancy, emphasizing the need for further research to advance understanding of female-specific neurobiology and to develop targeted interventions that support healthy eating behaviors, ultimately improving maternal and offspring health outcomes.

Throughout human history, pathogens have exerted great pressure on human genome that have defined susceptibility to both infectious and autoimmune diseases. This is possible because both type of conditions share susceptibility loci. The emergence of novel technologies that improves the genome analysis has greatly enhanced our ability to characterize in deeper the genetic architecture of human susceptibility to infectious diseases and autoimmune conditions. These genetic data sets identify outstanding informative overlaps that point to genetic modulation of immune function and inflammatory responses that affects both types of conditions. In this work, we revised single nucleotide polymorphisms and other genetic variations shared between these two categories of disease.

Omics technologies are transforming our understanding of disease mechanisms and reshaping clinical practice. By enabling high-throughput, unbiased data collection at various molecular levels - including genes (genomics), mRNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics) - omics approaches offer a comprehensive view of biological states in both health and disease. Among these, metabolomics has emerged as a pivotal tool, rapidly evolving beyond diagnostics to become a cutting-edge technique for pinpointing metabolites that regulate key physiological processes. This chapter reviews the advances in metabolomics, its integration with other omics approaches, and its applications, particularly emphasizing energy homeostasis. By incorporating metabolomic insights into physiology, we move closer to an integrative understanding of biological systems, laying the groundwork for novel therapies to combat obesity and related metabolic disorders.

Prader-Willi syndrome (PWS) is a complex genetic disorder arising from abnormalities on chromosome 15q11.2-q13, characterized by distinct physical, cognitive, and behavioral features that evolve across the lifespan. Early manifestations include severe hypotonia, feeding difficulties, and failure to thrive in infancy, progressing to hyperphagia, obesity, intellectual disabilities, and behavioral challenges in later stages. Additional features include growth hormone deficiency, short stature, delayed puberty, and other endocrine abnormalities. Genetic advances have illuminated the role of imprinted genes, such as SNORD116, in driving the syndrome's core features, offering insights into its variability and severity. Emerging research on targeted pathways, including oxytocin and ghrelin signaling, holds promise for innovative treatments addressing hyperphagia and behavioral symptoms. This chapter provides a comprehensive overview of PWS's clinical features, natural history, and molecular underpinnings, underscoring the importance of early diagnosis, multidisciplinary care, and precision medicine in optimizing outcomes and enhancing the quality of life for individuals with PWS.

Complex traits, characterized by their reliance on multiple genetic variants and intricate environmental influences, present a unique challenge in the field of genetics. At the core of complex traits lies the interaction between numerous genetic variants-often polygenic in nature-and their regulation through epigenetic mechanisms. These mechanisms, which include DNA methylation, histone modification, and non-coding RNA activity, play a crucial role in gene expression and can significantly influence phenotypic outcomes. By examining how genetic and epigenetic elements interact, we can gain insight into the biological processes that underlie variation in complex traits. Ultimately, this chapter seeks to provide a comprehensive framework for understanding the multifaceted relationships between genetic and epigenetic factors in complex traits. By unraveling these interactions, we hope to pave the way for future research that can inform strategies for improving health outcomes and clinical practices.

Thermoregulation is a fundamental biological process that allows birds and mammals to maintain a stable internal temperature despite environmental fluctuations, a mechanism shaped by millions of years of evolution. Non-shivering thermogenesis (NST), primarily driven by brown adipose tissue (BAT), plays a central role in thermoregulation by not only helping maintain energy homeostasis but also influencing broader metabolic and physiological processes. Recent research has revealed that BAT thermogenesis is regulated by peripheral hormones and at a central level, with key hypothalamic energy-sensing pathways-such as AMP-activated protein kinase (AMPK) and endoplasmic reticulum (ER) stress-playing critical roles. Beyond its metabolic functions, BAT and NST have emerged as important contributors to tumor biology, offering novel therapeutic strategies for metabolic and oncological diseases. This review explores the intricate mechanisms underpinning NST, including UCP1-dependent thermogenesis and alternative pathways such as creatine cycling, calcium-dependent thermogenesis, and lipid cycling. Emerging evidence further highlights BAT's potential in to modulate tumor metabolism, with pharmacological and genetic approaches showing promise in reshaping the tumor microenvironment. This growing body of knowledge offers exciting prospects for targeting BAT thermogenesis in treating obesity and other metabolic diseases.